The major objective of this research proposal is to study radiation-induced thyroid cancer by a coordinated program of clinical and basic endocrinological investigations. The clinical studies are designed to determine the current risk and continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approaches to treatment. This will be accomplished by a longitudinal study of patients who have been evaluated at Michael Reese Hospital because of a history of childhood head and neck irradiation. Of 5,200 patients who were so treated, 1,700 have been examined and another 1,400 have been contacted. In this population there is a 32 percent prevalence of nodules and among those who have had surgery 36 percent have had thyroid cancer. Followup examination of patients who were initially normal will provide an estimate of the continuing incidence of radiation-induced thyroid cancer. Followup examination of patients who were initially abnormal will provide an evaluation of the various methods of treatment which have been used. Together these will provide the information necessary to develop clinical guidelines for the care of persons with a history of head or neck irradiation. Laboratory studies will focus on the role of serum thyroglobulin in the diagnosis of thyroid tumors. Plasma thyroglobulin is elevated in a majority of patients with thyroid nodules and in 12 percent of patients with a history of irradiation but who otherwise appear completely normal. This project will determine whether an elevated thyroglobulin level indicates an especially high risk for the formation of thyroid nodules and study the role of serum thyroglobulin measurements in managing patients with thyroid cancer. Detailed studies of the molecular properties of serum thyroglobulin using physical-chemical methods will continue in order to improve its diagnostic usefulness and to understand how it enters the circulation. The mechanisms controlling thyroglobulin synthesis and secretion will be studied by perifusion of isolated thyroid cells and follicles. The Wollman transplantable thyroid tumor line 1-1C2 will be used as a model system to study plasma thyroglobulin and thyroid cancer.